Complement and diverse enrichment of antibodies in intraluminal thrombi from abdominal aortic aneurysms may contribute to increased inflammation

Abstract

Abstract Abdominal aortic aneurysms (AAA) often contain an intraluminal thrombus (ILT) which may contribute to aneurysm growth and rupture, but the mechanisms are not well understood. We hypothesized that complement and antibodies play a central role in the immune reactions within ILT from AAA. We quantified pre-specified proteins from complement and other defense systems, including coagulation, fibrinolysis, neutrophils, relevant proteinases and inhibitors, as well as immunoglobulins in ILT ( n  = 7), using fresh thrombi for comparison ( n  = 7). Protein analysis was performed using liquid chromatography in tandem with mass spectrometry, permitting simultaneous protein detection with comparable quantitative results, and antibody diversity characterization. The results indicated complement activation (classical and lectin pathways), coagulation (contact pathway), and degranulation including proteinase release from neutrophils in the ILT, with protein enrichment compared to fresh thrombi. Inhibitors of these systems were also present. In the ILT, 151 different immunoglobulin heavy chain and 144 different light chain variable regions were detected. Corresponding numbers in the controls were 25 and 26. Immunohistochemistry confirmed terminal complement activation and substantial presence of IgG in the ILT, which also contained IgM and IgA. These results are suggestive of a complex immunological process with activation of many defense systems, and antibody enrichment in the ILT.